肝细胞癌亚细胞器蛋白质组学初步探讨

The preliminary study on proteomics of hepatocellular carcinoma of the subcellular level

目的通过双向电泳技术和MALDI-TOF/MS分析,分别进行肝癌(HCC)组织与正常肝组织的细胞质与细胞核蛋白质谱的差异表达研究(在细胞质与细胞核水平分析HCC与正常肝组织的蛋白表达差异),分析差异表达蛋白与肝癌发生的关系,发掘一些与肝癌发生相关的标记物。方法取12例肝癌手术切除的新鲜的癌组织和正常肝组织,进行双向电泳,PDQuest软件筛选差异显著的蛋白质点,MALDI-TOF/MS质谱仪鉴定差异蛋白,并对差异蛋白进行功能分类,推测其可能的致病机制。结果①肝癌组织与正常组织的细胞质蛋白表达差异:有统计学差异(P<0.05)的差异蛋白点共有31个,其中在癌组织中表达上调(>2倍)的有18个,下调(>2倍)的有13个。这些差异蛋白主要与凋亡、细胞骨架、分泌跨膜蛋白等相关;②肝癌组织与正常组织的细胞核蛋白表达差异:有统计学差异(P<0.05)的差异蛋白点共有27个,其中在癌组织中表达上调(>2倍)的有14个,下调(>2倍)的有13个。这些差异蛋白主要与细胞增殖、蛋白迁移等相关。结论 Actin,cytoplasmic 1和Ras相关蛋白可能是潜在的肝癌标记物,深入研究这些蛋白质,可能为肝癌的发生机制和干预治疗研究提供新的靶点。

Objective To analyze the protein expression difference between hepatocellular carcinoma （HCC） tissue and normal liver tissue in the level of the cytoplasm and nucleus, to identify the differentially expressed proteins, and analyze the relationship between the differentially expressed proteins and HCC. Methods Twelve cases of fresh HCC tissue and normal liver tissue were collected, the proteing differences was analyzed by the way of 2D electrophoresis and PDQuest software, and the difference proteins were identified with the MALDI TOF/ TOF mass spectrometry. Results ① Cytoplasm protein expression difference between HCC liver cancer tissue and normal tissue： there were 31 proteins with significant difference （P〈0.05）, including 18 up-regulated （〉2-fold） and 13 down-regulated （〉2-fold） in the HCC tissues; these proteins were mainly related to apoptosis, cytoskeleton, secretion of transmembrane proteins. ②Nuclear protein expression difference between HCC liver cancer tissue and normal tissue： there were 27 proteins with significant difference （P〈0.05）, including 14 up-regulated （〉2-fold） and 13 down-regulated （〉2-fold） in the HCC tissues; these proteins were mainly related to cell proliferation, protein migration. Conclusion Actin, cytoplasmic I and Ras-related protein may be the potential tumor markers, in-depth study of these proteins may provide a new target for the occurrence mechanisms of HCC and intervention treatment.